Lymphocytic choriomeningitis (LCM) virus, inoculated into neonatal rats, produces an acute and nonfatal necrotic lesion of the cerebellum, with resulting permanent ataxia. Other arenaviruses (Tacaribe and Tamiami) cause destructive lesions of cerebellum and other brain nuclei in neonatal mice. All of these lesions are immunologically mediated, as indicated by the sparing effects of ALS or thymectomy and the aggravating effects of adoptive immunization. These models, delineated by prior work in this laboratory, provide a superb opportunity to study in detail prototype of virus-induced immunopathology. Proposed studies will exploit these convenient and reproducible models to: (1) Dissect the immunological mechanisms of disease production, utilizing a broad range of techniques; (a) fractionation of T-lymphocytes, B-lymphocytes, and mononuclear phagocytes; (b) in vivo adoptive immunization; (c) in vitro assay of cell-mediated immunity; (d) electronmicroscopy; (e) immunohistochemistry; and (f) radioisotopic labelling of leukocyte subpopulations. (2) Analyse the longterm aberrations in growth and development of the central nervous system produced by neonatal arenavirus infection, utilizing histological, chemical, and behavioral methodology. BIBLIOGRAPHIC REFERENCES: del Cerro, M., Nathanson, N., and Monjan, A.S. Pathogenesis of cerebellar hypoplasia produced by LCM virus infection of neonatal rats. 2. An ultrastructural study of the immune-mediated pathology. Lab Invest., 33:608-617, 1975. Nathanson, N., Monjan, A.A., Panitch, H.S., Johnson, E.D., Petursson, G., and Cole, G.A. Virus-induced cell-mediated immmunopathological disease, in A. L. Notkins, ed., Viral Immunology and immunopathology, New York: Academic Press, 1975, pp. 357-391.